Pauws E, Tummers R F, Ris-Stalpers C, de Vijlder J J, Voûte T
Department of Pediatric Endocrinology G2-106, Academic Medical Center, University of Amsterdam, Emma Children's Hospital, AMC, Amsterdam, The Netherlands.
Med Pediatr Oncol. 2001 Jun;36(6):630-4. doi: 10.1002/mpo.1140.
Characterization of the genetic background of pediatric thyroid carcinomas could aid in distinguishing between differently staged tumors with respect to treatment and prognosis. Two known genetic factors associated with thyroid carcinoma, the proto-oncogenes gsp and ras were investigated.
DNA was extracted from paraffin sections from both tumor and normal thyroid tissue of nine patients (ages 9-16 years). Of these patients, eight were diagnosed with papillary carcinoma and one with follicular adenoma. The coding exons of gsp and the three known ras genes (H, K, and N-ras) were screened for mutations using SSCP-analysis.
There were no mutations present in the ras and gsp proto-oncogenes hot spots, however, LOH of H-ras (chromosome location 11p15.5) was found in tumor tissue from one patient and a homozygous mutation in exon 12 of gsp causing a Pro-->Ser conversion was present in the thyroid tumor tissue from another patient. Two silent polymorphisms were detected, H-ras exon1, 86T-->C and gsp exon 5, 81T-->C.
Our results indicate that the ras/gsp mutations found are probably late events in the tumorigenesis representing general oncogenic stress. In conclusion, it seems that ras/gsp activation is not a factor in the mechanism causing sporadic thyroid carcinoma in children.
对儿童甲状腺癌的遗传背景进行特征分析有助于区分不同分期的肿瘤，从而指导治疗和判断预后。研究了两个与甲状腺癌相关的已知遗传因素，即原癌基因gsp和ras。
从9名患者（年龄9 - 16岁）的肿瘤及正常甲状腺组织的石蜡切片中提取DNA。这些患者中，8例被诊断为乳头状癌，1例为滤泡性腺瘤。使用单链构象多态性分析（SSCP分析）筛查gsp的编码外显子以及三个已知的ras基因（H、K和N - ras）的突变情况。
ras和gsp原癌基因热点区域未发现突变，然而，在一名患者的肿瘤组织中发现H - ras（染色体定位11p15.5）存在杂合性缺失，在另一名患者的甲状腺肿瘤组织中gsp外显子12存在纯合突变，导致脯氨酸（Pro）转变为丝氨酸（Ser）。检测到两个沉默多态性，H - ras外显子1，86T→C和gsp外显子5，81T→C。
我们的结果表明，所发现的ras/gsp突变可能是肿瘤发生过程中的晚期事件，代表一般的致癌应激。总之，ras/gsp激活似乎不是儿童散发性甲状腺癌发病机制中的一个因素。
